The respiratory distress syndrome (RDS) remains a major cause of morbidity and morality for premeture infants. While inadequate surfactant contributes to the pathophysiology of RDS, very little is known about surfactant phospholipid metabolism during the course of RDS. Also, our studies have demonstrated the presence of inhibitors of surfactant function in the airways of premature lambs, and rapid clearance of an artificial surfactant from the airways. Preliminary data identify inhibitors in the airways of infants with RDS While surfactant replacement therapy improves lung function in premature humans and animals, very little is known about the metabolism of exogenously administered surfactant. We will study a number of basic aspects of surfactant metabolism using prematurely delivered lambs at 120 and 134-136 days gestational age supported on infant ventilators and cared for as infants with RDS. We will measure airway phospholipid pool size, airway clearance of tracer doses of radiolabeled natural surfactant, surface activity, and the presence of surfactant inhibitors in the airways and correlate these with the degree of lung immaturity present in the animal. We will define the effects of several secondary phenomena associated with lung immaturity (increased premeability of the airways to protein and the patent ductus arteriosus (PDA) on surfactant metabolism. We will study the response of lambs to surfactant treatments, the clearance from the airways of exogenously administered radioactive natural and artificial surfactants, the effect of surfactant inhibitors on these surfactants, the effect of surfactant therapy permeability characteristics and the PDA, and the distribution of surfactant used for treatment within the airways. We will characterize and purify surfactant inhibitors from the airways of premature lambs and describe the surface activity changes and surfactant inhibitory activities present in airway samples from infants with RDS. Finally, we will characterize the subcellular metabolism of surfactant phospholipids in fetal lambs. These studies will be directed toward defining surfactant phospholipid metabolism and function during RDS.